Intranephron localization and regulation of the V1a vasopressin receptor during chronic metabolic acidosis and dehydration in rats

Abstract.

The intrarenal localization and role of the V1a vasopressin receptor in body fluid homeostasis are unclear. We investigated the intranephron localization of V1a receptor mRNA and protein using reverse transcription (RT)-competitive polymerase chain reaction (PCR) and immunohistochemistry with a specific polyclonal antibody. To determine whether the V1a receptor is involved in the regulation of acid-base balance, we also examined the effects of acute and chronic metabolic acidosis and dehydration on V1a receptor expression. V1a mRNA was expressed most abundantly in the cortical collecting ducts (CCD) and decreased in the deeper CD. Expression in the glomeruli and thick ascending limbs was low. The immunohistochemical study revealed the presence of the V1a receptor in the glomeruli, the thick ascending limbs and the CD. Dehydration decreased V1a mRNA expression in the CD. Chronic metabolic acidosis increased V1a receptor mRNA expression in the CD but decreased V2 receptor mRNA expression. Western blot analysis revealed up-regulation of the V1a receptor protein in chronic metabolic acidosis. Incubation of microdissected CCD or outer medullary CD (OMCD) in a low-pH (or or low-HCO₃ ^–) medium increased the levels of V1a receptor mRNA but decreased V2 receptor mRNA expression. Incubating OMCD with arginine vasopressin (AVP) and the V1a receptor antagonist (OPC21268) increased V2 receptor mRNA expression compared with incubation with AVP alone. These data suggest that V1a receptors are present primarily in the principal and intercalated cells in the CD and that these receptors are involved in the regulation of water and acid-base balance.